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40 Cards in this Set
- Front
- Back
Where are the HLA/MHC genes found in humans?
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Chromosme #6
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Identify the three types of MHC molecules and where they are found.
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Class I: most nucleated cells
Class II: professional APCs (m + B + dc) Class III: secreted proteins found in serum |
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MHC I genes present to ____?
Gene locus is ____? |
CD8+ Tcells (ex. Tc)
HLA-A, B & C in humans |
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MHC II genes present to ____?
Gene locus is ____? |
CD4+ Tcells (Th)
HLA-DP, HLA-DQ, HLA-DR in humans |
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HLA definition
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A gene product of the major histocompatibility complex; these antigens have been shown to have a strong influence on human allotransplantation, transfusions in refractory patients, and certain disease associations.
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MHC III genes present to____?
Gene locus is ____? |
do not directly present Ag to Tcells
code for: complement Pr- cytokines (TNF) Ag processing Pr- (TAP, LMP2 & LMP7) |
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What is the difference between MHC I and MHC II?
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I = single chain pr- associated with 2nd pr- not encoded for by MHC locus (beta2)
II: heterodimers coded for by the alpha and beta genes encoded within MHC locus |
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what is the beta 2 microglobulin?
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the protein located within MHC I (an invariant chain) located on chromosome 15. it is the "crutch" which holds the Ag peptide area out to the Tcell
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haplotype definition:
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The alleles found on a single chromosome present at the known polymorphic sites in a gene or region of genomic DNA. The two haplotypes of a gene carried by an individual are that individual's alleles for the gene.
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how many MHC I variants are there?
MHC II? |
6 different MHC I
12 different MHC II |
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why are MHC proteins considered to be highly polymorphic?
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1. co-dominant, both alleles expressed at once.
2. closely linked, low recombination frequency. 3. both alleles provide haplotype |
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why are MHC genes considered to be polygenic?
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1. multiple similar genes
2. 6 class I and 12 class II a. multiple dr-beta genes found in one person, and each can associate with the same/different dr-alpha genes. this increases diversity. |
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define classical MHC genes v. non-classical
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c: T cell recognition of Ag
(HLA-a, b & c. HLA-dp, dr, dq) n: NK cells and others |
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will the progeny of inbred mice be able to donate a graft to its parents?
receive a graft from its parents? |
the progeny expresses BOTH haplotypes of the parents, so it can accept grafts from the parents. If the mother were to receive a graft from F1, it would be rejected as it contains the father's MHC.
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with no recombination, what are the odds that siblings will be histocompatible?
with recombination? |
25%
2% |
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what is the likelihood that two unrelated individuals have identical haplotypes?
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almost zero
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how does racial segregation affect this?
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tissue transplants often need to be from members of the same racial background, due to specific recombinations within that population.
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what is required within the MHC I molecule to bring it to the surface of the cell?
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association of the large alpha chain with the invariant beta-2 microglobulin (which has no actual interaction with the Ag)
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what are the three domains of the MHC I protein? what are their functions?
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alpha 1 & 2 form the peptide binding cleft (8-10 aa)
alpha 3 interacts with CD8. it is structurally similar to beta-2 (via Ig constant region)and is relatively invariable. |
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what is the structure and function of the MHC II protein?
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it's a heterodimer of alpha and beta chains, each is encoded for by different genes.
alpha 1/beta 1 = Ag binding cleft alpha 2/beta 2 = CD4 contact area |
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MHC proteins are highly polymorphic because: (3)
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1. co-dominant, both alleles expressed at once.
2. closely linked, low recombination frequency. 3. both alleles provide haplotype |
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MHC genes are polygenic because: (2)
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1. multiple similar genes
2. 6 class I and 12 class II a. multiple dr-beta genes found in one person, and each can associate with the same/different dr-alpha genes. this increases diversity. |
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define classical v. non-classical
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c: T cell recognition of Ag
(HLA-a, b & c. HLA-dp, dr, dq) n: NK cells and others |
|
will the progeny of inbred mice be able to donate a graft to its parents?
receive a graft from its parents? |
the progeny expresses BOTH haplotypes of the parents, so it can accept grafts from the parents. If the mother were to receive a graft from F1, it would be rejected as it contains the father's MHC.
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with no recombination, what are the odds that siblings will be histocompatible?
with recombination? |
25%
2% |
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what is the likelihood that two unrelated individuals have identical haplotypes?
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almost zero
|
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how does racial segregation affect this?
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tissue transplants often need to be from members of the same racial background, due to specific recombinations within that population.
|
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what is required within the MHC I molecule to bring it to the surface of the cell?
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association of the large alpha chain with the invariant beta-2 microglobulin (which has no actual interaction with the Ag)
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what are the three domains of the MHC I protein? what are their functions?
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alpha 1 & 2 form the peptide binding cleft (8-10 aa)
alpha 3 interacts with CD8. it is structurally similar to beta-2 (via Ig constant region)and is relatively invariable. |
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what is the structure and function of the MHC II protein?
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it's a heterodimer of alpha and beta chains, each is encoded for by different genes.
alpha 1/beta 1 = Ag binding cleft alpha 2/beta 2 = CD4 contact area |
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is MHC Ag binding specific?
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NO. a given MHC can bind a variety of Ag peptides
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what is the difference between class I and II binding sites?
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class I is BLOCKED at ends, holds smaller peptides and anchors the residues at #2 and #9.
class II is OPEN at ends, holds larger peptides (13-18) and anchors aren't specific. negatively charged position at #4, hydrophobic at #9. |
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what types of peptides do MHC class I molecules present?
where do the Ag and MHC associate? |
endogenous peptides (ie viral)
Antigenic peptide and MHC I interact in the ER |
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how many MHC I molecules are present on the surface of a cell?
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10^5
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how many peptides are needed for recognition
what is their preferred chain length? |
100 for recognition.
nonamers are preferred (8-10) |
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which amino acids are usually recognized by the TCR?
what is their structure? which amino acids contact the MHC? |
4-7 are usually recognized by the TCR. they form a 'bulge'.
1/2 and 8/9 contact the MHC. |
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where is the greatest degree of variability found within the MHC I?
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alpha 1 & alpha 2 domains b/c they hold the antigenic peptide.
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what types of peptides do MHC class II molecules present?
how are the peptides degraded? |
they present exogenous peptides.
they are degraded via the endocytic pathway. |
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how large are the antigenic peptides bound by class II?
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at least 13 amino acids. 9 amino acids are within the cleft.
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what is the binding domain of class II? does the peptide bulge like in class I?
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the binding domain is alpha 1/beta 1. there is a lesser bulge present.
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